The metabolism of arachidonic acid is changed by dipyridamole in isolated hamster lungs.
14C-Arachidonate (50 nmol) was injected into the pulmonary circulation of isolated perfused lungs of female hamsters and the metabolites were analysed from the nonrecirculating perfusion effluent. Pulmonary infusion of dipyridamole (20 microM) increased the amount of radioactivity in the perfusion effluent of 0-4 min from 12.8 +/- 1.0% to 17.2 +/- 1.5% (2P less than 0.05) of the injected amount. Dipyridamole increased the amounts of PGF2 alpha, PGE2 and two unidentified metabolite groups in the effluent. An increasing trend was seen also in the amount of 6-keto-PGF1 alpha and TxB2. A decreasing trend was, however, seen in the amount of metabolites migrating near to unlabelled 15-keto-PGE2. When 20 nmol of 14C-PGE2 was injected into the pulmonary circulation of isolated hamster lungs, the amount of 15-keto-metabolites of PGE2 in the effluent was decreased and that of unmetabolized PGE2 increased by dipyridamole dose dependently. The rate of efflux of radioactivity from the lungs was increased by dipyridamole. Dipyridamole was in vitro not an inhibitor of 15-hydroxyprostaglandin dehydrogenase in the 100.000 supernatant fraction of homogenized hamster lungs. At 20 microM and 100 microM it even caused a slight in vitro activation of 15-hydroxyprostaglandin dehydrogenase. Thus the decreased pulmonary inactivation of PGE2 by dipyridamole is obviously due to the decreased uptake of PGE2 into the lungs. This could explain partly the detected changes in the pulmonary metabolism of arachidonic acid by dipyridamole.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001711:Biotransformation; D006224:Cricetinae; D004176:Dipyridamole / Q000494:pharmacology*; D005260:Female; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008647:Mesocricetus; D011458:Prostaglandins E / Q000378:metabolism
D001095:Arachidonic Acids; D011458:Prostaglandins E; D016718:Arachidonic Acid; D004176:Dipyridamole; D006911:Hydroxyprostaglandin Dehydrogenases